Background: The use of tranexamic acid (TXA) in total hip replacement (THR) typically reduces blood loss by approximately 400 mL, and typical total blood loss is still approximately 1 L. A barrier to harnessing the full potential of TXA is disagreement on the optimum timing of administration. To address this, we aimed to identify the period of greatest blood loss. Methods: We analyzed the perioperative data of 870 patients who had undergone THR, total knee replacement, or unicompartmental knee replacement just before the introduction of TXA to our unit. Total blood loss was calculated on postoperative day (POD) 1 and POD2 using an equation based on change in hematocrit. Results: Average total blood loss at POD2 was 1505, 1322, and 611 mL for THR, total knee replacement, and unicompartmental knee replacement, respectively. Between 86% and 96% of this blood loss occurred in the period between skin closure and POD1. Intraoperative loss did not correlate with total loss at POD2. Blood transfusion was more likely if the patient was female (odds ratio [OR], 6.8) or if they had preoperative anemia (OR, 8.3) than if there was a high-volume blood loss (OR, 1.6). Conclusions: Approximately 90% of blood loss occurs between skin closure and the first postoperative 24 hours. “Intraoperative blood loss” and “transfusion rate” are not reliable markers of total blood loss. The full potential of TXA could be harnessed by using it during the period of greatest blood loss, that is, during the first postoperative 24 hours. Keywords: Arthroplasty, Hip, Knee, Blood loss, Tranexamic acid